Review Question - QID 210117

The Jagged1-Notch pathway becomes activated by the action PTH.

Osteoblasts have been found to regulate hematopoietic stem cells and the immune response. They do this through the Jagged1-Notch pathway. PTH induces Jagged1, a membrane-bound protein, on osteoblasts. Jagged1 stimulates Notch receptors on the membrane of hematopoietic stem cells (HSC). This stimulation leads to cell proliferation of HSC.

Lorenzo et al. performed a review of interactions of bone and the immune system. Thy report that stimulation of the PTH receptor on bone cells increased the number of HSC in bone marrow. This also increased the levels of Jagged1 on osteoblasts. This effect was blocked by using inhibitors of Notch signaling. They conclude that PTH directly stimulates the production of Jagged1 by osteoblasts.

Weber et al. performed a study which demonstrated that activation of the PTH receptor in osteoblasts activates the Jagged1-Notch pathway and expands HSC. They found that PTH treatment increases Jagged1 levels in osteoblastic cells in vivo and in vitro. They conclude that since Jagged1-Notch signaling has been implicated in HSC interactions and osteoblastic differentiation, this pathway may play a critical role in mediating the PTH-dependent expansion of HSC, as well as the anabolic effect of PTH on bone.

Illustration A is demonstrating PTH's effects. PTH activates numerous cytokines and other mediators on osteoblasts (OBs), osteoclasts (OCs), bone marrow mesenchymal stem cells (MSCs), and hematopoietic stem cells (HSCs) located close to the endosteal niche.

Incorrect Answers:
Answers 1, 2, 3, & 4: The Jagged1-Notch pathway becomes activated by the action of PTH. None of the listed mediators have been implicated in this pathway.